Several years' study of T-cell and B-cell differentiation has led to the description of discrete sets of T-cells, and B-cells, and respective precursor populations. These can be distinguished by allotypic markers which characterize the surface phenotype of the respective sets. These sets differ in functional properties, and in the specificity of inducers that move them from one compartment of differentiation to the next. Another marker of lymphocyte differentiation is the template independent DNA polymerase, terminal deoxynucleotidyl transferase (TdT), which because of its unique biochemistry and tissue distribution, has been proposed as a mediator of generating the diversity of idiotypes in mature lymphocytes. We propose to examine the sequential and divergent differentiative steps of the lymphocyte lineage by determining the programming of expresson of TdT in thymus and bone marrow using biosynthetic and immunofluorescent assays for TdT and immunofluorescent and rosetting assays for allotypic markers. We propose to create tumor analogues for pre-T and pre-B cells in which TdT biosynthesis can be induced, by constructing hybridomas. These will be used to identify new allotypic markers and to study the molecular biology of TdT induction, both in terms of signals for induction, and alterations of cellular DNA upon induction. We also propose to define the phenotype and resulting aberrant programming of lymphoid cells sets transformed by Abelson Murine Leukemia Virus, and by chemical carcinogen treatment of liquid bone marrow cultures. Such systems will create the tools to study the biochemistry of a program block in lymphocyte differentiation.